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- Title
Adipocyte-specific overexpression of FOXC2 prevents diet-induced increases in intramuscular fatty acyl CoA and insulin resistance.
- Authors
Kim, Jason K.; Hyo-Jeong Kim; Park, So-Young; Cederberg, Anna; Westergren, Rickard; Nilsson, Daniel; Higashimori, Takamasa; You-Ree Cho; Zhen-Xiang Liu; Jianying Dong; Cline, Gary W.; Enerback, Sven; Shulman, Gerald I.; Kim, Hyo-Jeong; Cho, You-Ree; Liu, Zhen-Xiang; Dong, Jianying
- Abstract
Insulin resistance plays a major role in the development of type 2 diabetes and may be causally associated with increased intracellular fat content. Transgenic mice with adipocyte-specific overexpression of FOXC2 (forkhead transcription factor) have been generated and shown to be protected against diet-induced obesity and glucose intolerance. To understand the underlying mechanism, we examined the effects of chronic high-fat feeding on tissue-specific insulin action and glucose metabolism in the FOXC2 transgenic (Tg) mice. Whole-body fat mass were significantly reduced in the FOXC2 Tg mice fed normal diet or high-fat diet compared with the wild-type mice. Diet-induced insulin resistance in skeletal muscle of the wild-type mice was associated with defects in insulin signaling and significant increases in intramuscular fatty acyl CoA levels. In contrast, FOXC2 Tg mice were completely protected from diet-induced insulin resistance and intramuscular accumulation of fatty acyl CoA. High-fat feeding also blunted insulin-mediated suppression of hepatic glucose production in the wild-type mice, whereas FOXC2 Tg mice were protected from diet-induced hepatic insulin resistance. These findings demonstrate an important role of adipocyte-expressed FOXC2 on whole-body glucose metabolism and further suggest FOXC2 as a novel therapeutic target for the treatment of insulin resistance and type 2 diabetes.
- Subjects
INSULIN resistance; FAT cells; TRANSCRIPTION factors; TRANSGENIC mice; TYPE 2 diabetes; ANIMAL experimentation; CELLULAR signal transduction; COENZYMES; COMPARATIVE studies; FAT content of food; GENE expression; INSULIN; RESEARCH methodology; MEDICAL cooperation; MICE; PROTEINS; RESEARCH; DNA-binding proteins; EVALUATION research; SKELETAL muscle; METABOLISM
- Publication
Diabetes, 2005, Vol 54, Issue 6, p1657
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.54.6.1657